Background PTPN22 is a protein phosphatase regulating negatively T-cell activation and participates in BCR signaling pathways. C1858T single nucleotide polymorphism (SNP) in PTPN22 encoding the R620W allele variant has been associated with autoimmunity as it leads to increased levels of auto reactive immature B cells, reduced BCR signaling and fewer B cells deletion. Genetic data strongly support the link between C1858T SNP and susceptibility to a number of autoimmune diseases including SLE, RA, type 1 diabetes, and auto immune thyroiditis.
Objectives We analyzed the effects of functional PTPN22 C1858T polymorphism (rs2476601) on rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) susceptibility in a in a group of Algerian affected patients.
Methods We conducted a case-control study including 676 samples from 299 RA, 152 SLE patients compared to 225 sex-, age-, and ethnicity-matched healthy controls. The TaqMan allele discrimination assay was used for sample genotyping. Screening and characterization of autoantibody [Anti-nuclear antibodies (ANA), Anti-citrullinated peptide antibodies (ACPA) and Rheumatoid Factor (RF)] specificities were performed using immuno-assay tests.
Results Our results showed a significant association between either 1858T allele (OR =3.34, 95% CI =1.06-12.38, pc =0.03) or 1858CT genotype (OR =3.43, 95% CI =1.07-12.83, pc =0.03) and susceptibility to SLE. However, no significant association was observed between this polymorphism and RA. Furthermore, after stratification according to autoantibody positivity, we found an association with either LES anti-dsDNA positive patients (pc =0.005) or LES anti-Ro/SSA60KDa positive patients (pc =0.01) compared with healthy controls. No association was found with positivity of ACPA and RF positive patients.
Conclusions Our results suggest that the PTPN22 1858T allelic variant is associated with genetic susceptibility to SLE but not of RA in the Algerian population, and that it may contribute also to anti-dsDNA and anti-Ro/SSA60KDa autoantibody production.
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Disclosure of Interest None declared
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